The Role of Botulinum Toxin Type A in the Clinical Management of Refractory Anterior Knee Pain.

Singer BJ, Silbert BI, Silbert PL, Singer KP - Toxins (Basel) (2015)

Bottom Line:
Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits.Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking.The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective.

ABSTRACTAnterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional "denervation" which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.

toxins-07-03388-f004: A significant change (*) in VM muscle activation compared to baseline (W0), during static maximal knee extensor contraction at 30° knee flexion, was seen in the BoNT-A injected group only by week 2 (W2) and was sustained at week 12 (W12) (#). The dotted line represents a normal ratio of VL:VM activation as assessed from surface EMG. Surface EMG from one subject highlights the relative reversal of VL and VM activation profiles seen in BoNT-A injected subjects only at week 2 (W2) post-injection. Reprinted with permission from [45]. Copyright 2011 BMJ Publishing Group Ltd.

Mentions:
In a subsequent double blinded, placebo injection controlled trial by the same group [45], 24 individuals with refractory AKP (mean duration 6 years) were randomly allocated to receive 500 U Dysport® (n = 14) or the same volume placebo (n = 10) injection to the distal area of the VL muscle, again using EMG guidance to confirm placement. Prior to randomization, in addition to clinical evaluation, VL:VM muscle imbalance was derived from surface EMG recordings during isometric knee extension in 30° flexion. Abnormal VL:VM ratios from surface EMG during a stair climbing task, in addition to self-reported pain (at least 2/10) on provocative tasks such as squatting or stairs, have been shown to be a highly sensitive and specific way of identifying people with AKP [50]. Individuals who did not meet a priori criteria for quadriceps imbalance were not included in this trial. All subjects also met the exclusion criteria outlined for the open label pilot study above [43]. Enrolled subjects were again a relatively young group, with a mean age of 29.5 years (range 15–48 years). Mean baseline Anterior Knee Pain Scale (AKPS) scores (BoNT-A group 65/100; placebo 69/100) indicated moderate pain and disability [51]. Following intramuscular BoNT-A or same volume placebo injection and a twelve week individualized home exercise program, BoNT-A injected subjects demonstrated significantly greater improvement in knee pain and disability (measured using the AKPS) compared with those receiving placebo injection (p < 0.03), as well as reporting increased participation in sporting and daily living activities. Mean change in the experimental group exceeded the minimal clinically important difference (14 points) [52] for the AKPS (Figure 3). Statistically significant differences from baseline in self-reported pain (assessed using a visual analogue scale) during pain provoking activities were demonstrated only in the group who received BoNT-A injection (Figure 3). The ratio of VL:VM activation during an isometric quadriceps contraction was reversed at 2 weeks post injection (in the BoNT-A group) and remained significantly different from baseline at all time-points post injection (p < 0.001) (Figure 4). Subtle changes in ratio for the placebo group may have reflected the influence of the exercise intervention. Static quadriceps muscle force production at 30° knee extension was maintained or improved in BoNT-A injected subjects, despite focal atrophy of the distal component of VL muscle in the treated limb (Figure 5A), supporting the hypothesis that temporarily reducing VL activity would “dis-inhibit” the VM muscle. No measureable change in patellofemoral joint alignment was found from repeated CT assessment at 12 weeks despite the focal distal atrophy of VL muscle (Figure 5B). Subjective and objective improvements in BoNT-A injected subjects were maintained at the 24 week follow-up [45]. In phase two of this study, prior to unmasking of the data, five subjects elected to receive open label injection of BoNT-A, on the basis that they believed their symptoms were unchanged. Upon unmasking of the data, all of these subjects were subsequently found to have received placebo injection in phase one, and most subsequently reported clinically significant improvement following open label BoNT-A injection.

toxins-07-03388-f004: A significant change (*) in VM muscle activation compared to baseline (W0), during static maximal knee extensor contraction at 30° knee flexion, was seen in the BoNT-A injected group only by week 2 (W2) and was sustained at week 12 (W12) (#). The dotted line represents a normal ratio of VL:VM activation as assessed from surface EMG. Surface EMG from one subject highlights the relative reversal of VL and VM activation profiles seen in BoNT-A injected subjects only at week 2 (W2) post-injection. Reprinted with permission from [45]. Copyright 2011 BMJ Publishing Group Ltd.

Mentions:
In a subsequent double blinded, placebo injection controlled trial by the same group [45], 24 individuals with refractory AKP (mean duration 6 years) were randomly allocated to receive 500 U Dysport® (n = 14) or the same volume placebo (n = 10) injection to the distal area of the VL muscle, again using EMG guidance to confirm placement. Prior to randomization, in addition to clinical evaluation, VL:VM muscle imbalance was derived from surface EMG recordings during isometric knee extension in 30° flexion. Abnormal VL:VM ratios from surface EMG during a stair climbing task, in addition to self-reported pain (at least 2/10) on provocative tasks such as squatting or stairs, have been shown to be a highly sensitive and specific way of identifying people with AKP [50]. Individuals who did not meet a priori criteria for quadriceps imbalance were not included in this trial. All subjects also met the exclusion criteria outlined for the open label pilot study above [43]. Enrolled subjects were again a relatively young group, with a mean age of 29.5 years (range 15–48 years). Mean baseline Anterior Knee Pain Scale (AKPS) scores (BoNT-A group 65/100; placebo 69/100) indicated moderate pain and disability [51]. Following intramuscular BoNT-A or same volume placebo injection and a twelve week individualized home exercise program, BoNT-A injected subjects demonstrated significantly greater improvement in knee pain and disability (measured using the AKPS) compared with those receiving placebo injection (p < 0.03), as well as reporting increased participation in sporting and daily living activities. Mean change in the experimental group exceeded the minimal clinically important difference (14 points) [52] for the AKPS (Figure 3). Statistically significant differences from baseline in self-reported pain (assessed using a visual analogue scale) during pain provoking activities were demonstrated only in the group who received BoNT-A injection (Figure 3). The ratio of VL:VM activation during an isometric quadriceps contraction was reversed at 2 weeks post injection (in the BoNT-A group) and remained significantly different from baseline at all time-points post injection (p < 0.001) (Figure 4). Subtle changes in ratio for the placebo group may have reflected the influence of the exercise intervention. Static quadriceps muscle force production at 30° knee extension was maintained or improved in BoNT-A injected subjects, despite focal atrophy of the distal component of VL muscle in the treated limb (Figure 5A), supporting the hypothesis that temporarily reducing VL activity would “dis-inhibit” the VM muscle. No measureable change in patellofemoral joint alignment was found from repeated CT assessment at 12 weeks despite the focal distal atrophy of VL muscle (Figure 5B). Subjective and objective improvements in BoNT-A injected subjects were maintained at the 24 week follow-up [45]. In phase two of this study, prior to unmasking of the data, five subjects elected to receive open label injection of BoNT-A, on the basis that they believed their symptoms were unchanged. Upon unmasking of the data, all of these subjects were subsequently found to have received placebo injection in phase one, and most subsequently reported clinically significant improvement following open label BoNT-A injection.

Bottom Line:
Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits.Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking.The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective.

ABSTRACTAnterior knee pain is a highly prevalent condition affecting largely young to middle aged adults. Symptoms can recur in more than two thirds of cases, often resulting in activity limitation and reduced participation in employment and recreational pursuits. Persistent anterior knee pain is difficult to treat and many individuals eventually consider a surgical intervention. Evidence for long term benefit of most conservative treatments or surgical approaches is currently lacking. Injection of Botulinum toxin type A to the distal region of vastus lateralis muscle causes a short term functional "denervation" which moderates the influence of vastus lateralis muscle on the knee extensor mechanism and increases the relative contribution of the vastus medialis muscle. Initial data suggest that, compared with other interventions for anterior knee pain, Botulinum toxin type A injection, in combination with an active exercise programme, can lead to sustained relief of symptoms, reduced health care utilisation and increased activity participation. The procedure is less invasive than surgical intervention, relatively easy to perform, and is time- and cost-effective. Further studies, including larger randomized placebo-controlled trials, are required to confirm the effectiveness of Botulinum toxin type A injection for anterior knee pain and to elaborate the possible mechanisms underpinning pain and symptom relief.